眼内液细胞因子表达和高阶 OCT 生物标志物：在 IMAGINE DME 研究中评估解剖-生物标志物联系。
Aqueous Cytokine Expression and Higher Order OCT Biomarkers: Assessment of the Anatomic-Biologic Bridge in the IMAGINE DME Study.
机构信息
Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Retina Consultants of Houston, Retina Consultants of America, Houston, Texas, USA; Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas, USA.
出版信息
Am J Ophthalmol. 2021 Feb;222:328-339. doi: 10.1016/j.ajo.2020.08.047. Epub 2020 Sep 5.
PURPOSE
To identify biomarkers for predicting response to anti-vascular endothelial growth factor (VEGF) therapy in diabetic macular edema (DME) and evaluate any links between cytokine expression and optical coherence tomography (OCT) phenotype.
DESIGN
The IMAGINE is a post hoc image analysis and cytokine expression assessment of the Efficacy & Safety Trial of Intravitreal Injections Combined With PRP for CSME Secondary to Diabetes Mellitus (DAVE) randomized clinical trial.
METHODS
Subjects were categorized as anatomical responders or nonresponders, and within the responder group as rebounders and non-rebounders based on quantitative, longitudinal OCT criteria. Retinal layer and fluid features were extracted using an OCT machine-learning augmented segmentation platform. Responders were further sub-classified by rapidity of response. Aqueous concentrations of 54 cytokines were measured at multiple timepoints. Expression was compared between responder groups and correlated with OCT imaging biomarkers.
RESULTS
Of the 24 eyes studied, 79% were anatomical responders with 38% super responders, 17% early responders, and 25% slow responders. Twenty-one percent were nonresponders. Super responders had increased baseline vascular endothelial growth factor (VEGF) (880.0 pg/mL vs 245.4 pg/mL; P = .012) and decreased monocyte chemotactic protein-1 (MCP-1) (513.3 pg/mL vs 809.5 pg/mL; P = .0.042) concentrations compared with nonresponders. Interleukin-6 (-24.9 pg/mL vs 442.8 pg/mL; P = .032) concentrations increased among nonresponders during therapy. VEGF concentrations correlated with central subfield thickness (r = 0.49; P = .01). Panmacular retinal volume correlated with increased interleuckin-6 (r = 0.47; P = .02) and decreased MCP-1 (r = -0.45; P = .03). Matrix metallopeptidase-1 correlated with subretinal fluid volume (r = 0.50; P = .01).
CONCLUSIONS
OCT imaging biomarkers correlated with both intraocular cytokines and responsiveness to anti-VEGF therapy, which indicated a possible link to underlying pathways and their relevance to DME prognosis. Baseline concentrations of VEGF and MCP-1 are associated with anatomic response to anti-VEGF therapy.
目的
鉴定预测糖尿病性黄斑水肿（DME）对抗血管内皮生长因子（VEGF）治疗反应的生物标志物，并评估细胞因子表达与光相干断层扫描（OCT）表型之间的任何关联。
设计
IMAGINE 是一项事后图像分析和细胞因子表达评估，评估了玻璃体内注射联合 PRP 治疗糖尿病性黄斑水肿继发的中心性浆液性脉络膜视网膜病变（CSME）的疗效和安全性试验（DAVE）的随机临床试验。
方法
根据定量、纵向 OCT 标准，将受试者分为解剖学应答者和非应答者，在应答者组中进一步分为反弹者和非反弹者。使用 OCT 机器增强分割平台提取视网膜层和液体积聚特征。根据应答的速度，进一步对应答者进行亚分类。在多个时间点测量 54 种细胞因子的水相浓度。比较应答组之间的表达，并与 OCT 成像生物标志物相关联。
结果
在研究的 24 只眼中，79%为解剖学应答者，其中 38%为超应答者，17%为早期应答者，25%为缓慢应答者。21%为无应答者。与无应答者相比，超应答者的基线血管内皮生长因子（VEGF）水平升高（880.0 pg/mL 比 245.4 pg/mL；P =.012），单核细胞趋化蛋白-1（MCP-1）水平降低（513.3 pg/mL 比 809.5 pg/mL；P =.042）。在治疗期间，非应答者的白细胞介素-6（IL-6）浓度增加（-24.9 pg/mL 比 442.8 pg/mL；P =.032）。VEGF 浓度与中央视网膜厚度相关（r = 0.49；P =.01）。全视网膜容积与白细胞介素-6 增加相关（r = 0.47；P =.02），与 MCP-1 降低相关（r = -0.45；P =.03）。基质金属蛋白酶-1 与视网膜下液体积相关（r = 0.50；P =.01）。
结论
OCT 成像生物标志物与眼内细胞因子和对抗 VEGF 治疗的反应均相关，这表明与潜在途径之间存在可能的联系及其与 DME 预后的相关性。VEGF 和 MCP-1 的基线浓度与抗 VEGF 治疗的解剖学反应相关。
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